Tourette syndrome (TS) is caused by multiple genetic and environmental factors. Yet, little is known about the interplay of these factors in the occurrence of tics. We investigated whether polygenic risk score (PRS) of TS and pregnancy-related factors together enhance the explained variance of tic occurrence in the Avon Longitudinal Study of Parents and Children (N_cases = 612; N_controls = 4,201; 50% male; mean age 13.8 years). We included a cumulative adverse pregnancy risk score, maternal anxiety and depression, and maternal smoking and alcohol use during pregnancy. We investigated possible joint effects of genetic and pregnancy-related risk factors using a multivariable approach, and explored mediation effects between the pregnancy-related risk factors in explaining tic presence. The PRS and the cumulative adverse pregnancy risk score, maternal anxiety, or maternal depression explained significantly more variance of tic presence compared to models including only the PRS. Furthermore, we found that the cumulative adverse pregnancy risk score mediated the association between several pregnancy-related factors (maternal anxiety, depression, and smoking) and tics. The combination of a PRS and pregnancy-related risk factors explained more variance of tics in a general population cohort compared to studying these factors in isolation.

中文翻译：

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雅芳父母和儿童纵向研究中抽动的多基因和环境决定因素

抽动秽语综合症（TS）是由多种遗传和环境因素引起的。然而，人们对这些因素在抽动发生中的相互作用知之甚少。我们在雅芳家长和儿童纵向研究中调查了 TS 的多基因风险评分 (PRS) 和妊娠相关因素是否共同增强了抽动发生的解释方差（N 例 = 612；N 对照 = 4,201；50 %_为 男性；_平均 年龄13.8 年）。我们纳入了累积不良妊娠风险评分、母亲焦虑和抑郁以及母亲在怀孕期间吸烟和饮酒的情况。我们使用多变量方法研究了遗传和妊娠相关危险因素可能的联合影响，并探讨了妊娠相关危险因素之间在解释抽动存在方面的中介效应。与仅包含 PRS 的模型相比，PRS 和累积不良妊娠风险评分、产妇焦虑或产妇抑郁可以显着解释抽动存在的更多差异。此外，我们发现累积不良妊娠风险评分介导了几种妊娠相关因素（母亲焦虑、抑郁和吸烟）与抽动之间的关联。与单独研究这些因素相比，PRS 和妊娠相关危险因素的结合解释了一般人群队列中抽动的更多差异。